In mammals, interleukin-1.beta. (IL-1.beta.) is produced and released mainly by peripheral monocytes, such as macro-phages; interleukin-1.beta. converting enzyme (ICE), an enzyme that converts IL-1.beta. precursor protein (33 KD) to mature IL-1.beta. (17 KD), cleaves the Asp.sup.116 -Ala.sup.117 site in the precursor protein [N. A. Thornberry et al., Nature, Vol. 356, p. 768 (1992)]. IL-1.beta. is a cytokine having various functions, especially in the cells involved in inflammation or bone diseases. For example, it stimulates polynuclear leukocyte infiltration into inflammatory sites, increases the chemotaxis of macrophages etc., attracts them to the inflammatory sites, and induces their production of various prostaglandins etc., thereby changing the pathologic state. IL-1.beta. also exhibits potent action on bone-associated cells. In particular, it stimulates osteoclasts to considerably accentuate bone resorption. This cytokine is also profoundly involved in rheumatoid arthritis.
Recent evidence suggests the involvement of ICE in nerve cell apotosis [V. Gazliadni et al., Science, Vol. 264, pp. 820-828 (1994)].
On the other hand, cathepsin B is assumed to play a role in antigen processing in antigen-presenting cells [Y. Matsunaga, FEBS Letters, Vol. 324, pp. 325-330 (1994)]. In addition, cathepsin L is reportedly an important enzyme that decomposes bone substrate during bone resorption by osteoclasts [E. Kakegawa et al., FEBS Letters, Vol. 321, pp. 247-250 (1994)].
These enzymes are cysteine proteases especially associated with infectious diseases, immune diseases, bone diseases etc.; research has been undertaken on inhibitors for respective enzymes. With regard to ICE inhibitors, for example, since publication of the first report of Ac-Tyr-Val-Ala-Asp-H [N. A. Thornberry et al., Nature, Vol. 356, p. 768 (1992)], a peptide-derived inhibitor containing 3-amino-4-oxobutanoic acid at its C-terminal, peptide type inhibitors containing various aspartic acid derivatives, such as Ac-Tyr-Val-Ala-Asp-CH.sub.2 OC(O)Ar [N. A. Thornberry et al., Biochemistry, Vol. 33, pp. 3934-3940 (1994)], .gamma.-pyron-3-acetic acid [M. J. Salvatore et al., Journal of Natural Products, Vol. 57, pp. 755-760 (1994)] etc. have been reported. As concerns cathepsin B or L inhibitors, peptidyl (acyloxy) methyl ketones are reported by D. Bromme et al. in Biological Chemistry Hoppe-Seyler, Vol. 375, pp. 343-347 (1994) and by B. M. Wazner et al. in the Journal of Medicinal Chemistry, Vol. 37, pp. 1833-1840 (1994); norleucinal-containing peptide-derived inhibitors are reported in Japanese Patent Unexamined Publication No. 155764/1993; peptidyl phenoxymethyl ketones are reported in WO-9404172; leucinal-containing peptide-derived inhibitors are reported in Japanese published unexamined patent application No. 202170/1992; epoxysuccinic acid derivatives are reported in Japanese published unexamained patent application No. 304075/1990; and norleucinal-containing peptide-derived inhibitors effective against bone diseases are reported in Japanese published unexamined patent application No. 268145/1990. Also, Japanese publication of translations of International patent application 510986/1994 reports on a peptide compound having a glutamic acid derivative at its C-terminal as a picornavirus protease inhibitor; actually synthesized compounds as such include the following: ##STR5##